5780 phenylseleninic acid and further oxidation with hydrogen peroxide to benzeneperoxyseleninicacid, which brings about epoxidation of the tri-
Grieco, Y. Masaki, and D. Boxler. J. Am. Chem. SOC., 97, 1597 (1975). (19)P. A. Grieco, S. Gilman, and M. Nishizawa, J. Org. Chem., 41, 1485 (1976). (20)P. A. Grieco. J. A. Noguez, Y. Masaki, K. Hiroi, M. Nishizawa, A. Rosowsky, S. Oppenheim, and H. Lazarus, J. Med. Chem., 20, 71 (1977).
(21) The synthesis of lactone 31 and the conversion of its correspondingdiol to bisnorvernolepin and blsnorvernomenin has been reported [S.Danishefsky, T. Kitahara, P. F. Schuda, and S. Etheredge, J. Am. Chem. Soc., 98,3028(1976)]. Recently the conversion of bisnorvernolepinto vemolepin has appeared [S. Danishefsky,T. Kitahara, R . McKee, and P. F. Schuda, ui
substituted olefinic linkage. Details of this and other reactions will be reoorted shortlv.'5
(15)P. A:&ieco,'Y. Yokoyama, S.Gilman, and M. Nishizawa, J. Org. Chem., 42. 2034 11977). (16)The use of tertLbutyl hydroperoxide in benzene containing triton B has
-
previously been employed for epoxidation of a,@-unsaturatedenones [N. C. Yang and R. A. Flnnegan, J. Am. Chem. SOC., 80,5845 (1968)l.Our 23 in benzene solution resulted in complete attempts to convert 22 recovery of starting enone. (17)P. A. Grleco, K. Hlroi, J. J. Reap, and J. A. Noguez, J. Org. Chem., 40, 1450 11975). ~. -,(18) K. B. Sharpless and M. W. Young, J. Org. Chem., 40, 947 (1975);P. A.
.
ibid., 98,67 15j1976)J. (22)P. A. Grieco and K. Hiroi, J. Chem. SOC.,Commun., 1317 (1972). (23) P. A. Grieco, N. Marinovic, and M. Miyashita, J. Org. Chem.. 40, 1670 (1975). (24)The products were isolated by extraction of the aqueous layer with several
portions of the indicated solvent. The combined organic extracts were washed with water followed by saturated brine. The organic layer was usually dried with either anhydrous sodium sulfate or anhydrous magnesium sulfate. Filtration followed by removal of the solvent in vacuo (water aspirator) employing a rotary evaporator provided the products. (25)H. Bauer, f i r . , 48, 92 (1913).We have found that the crude crystalline material obtained from the procedure of Bauer can be sublimed At 100 ' C (0.2mmHg), providing yellow crystals of enitrophenyl selenocyanate, mp 144 ' C .
Marine Natural Products. Xenicin: a Diterpenoid Possessing a Nine-Membered Ring from the Soft Coral, Xenia elongata' D. J. Vanderah, P. A. Steudler, L. S. Ciereszko, F. J. Schmitz,* J. D. Ekstrand, and D. van der Helm* Contribution from the Department of Chemistry, University of Oklahoma, Norman, Oklahoma 73019. Received October 12, 1976
Abstract: T h e structure o f a new diterpenoid, xenicin ( l ) ,isolated f r o m a soft coral, Xenia elongata, has been determined by single crystal x-ray diffraction. Xenicin possesses a nine-membered carbocyclic r i n g trans-fused t o a dihydropyran ring. T h e crystals are monoclinic, space group C2, four molecules per unit cell w i t h dimensions a = 17.704 (3), 6 = 9.061 (2), c = 18.656 (4) A; = 113.33 (2)'. The intensity data (3015) were collected on an automatic diffractometer. The structure, determined by direct methods, was refined b y least-squares methods. T h e f i n a l R was 0.046 for a l l the data.
In our continuing research on the chemistry of soft corals (alcyonaceans) we have isolated a diterpenoid, xenicin (l), having a new skeleton in which the only carbocyclic ring present is nine membered. The cyclononene ring itself occurs in only one diterpenoid isolated previously* and among sesquiterpenoids is restricted to a few compounds related to ~aryophyllene.~ Other investigationsof soft corals have resulted in the discovery of new sesquiterpene^,^ d i t e r p e n e ~and , ~ ster o k 6 The diterpenes previously reported from alcyonaceans have a cembrene ~ k e l e t o nor ~ ~one - ~easily derived from it by cyclization.5g
Results and Discussion Xenicin, mp 141.5-142.3 "C, [ ( Y ] * ~ . ~-36.7" D (0.6, CHC13), was obtained by adsorption chromatography from the hexane soluble portion of an aqueous 2-propanol extract of Xenia elongata collected near Heron Island, Australia. Interestingly, specimens of X . elongata from Picnic Bay, Magnetic Island, Australia and from the Fiji Islands did not contain any of this new diterpenoid. High resolution mass spectral and elemental analysis established the formula C28H3809for 1. Its infrared spectrum lacked hydroxyl absorption, but displayed a strong, broad band centered at 1735 cm-I (acetate) with a shoulder at 1700 cm-'. The N M R spectrum contained signals for four acetates and three vinyl methyl groups in addition to downfield multiplets corresponding to nine protons from which some Journal of the American Chemical Society
partial structural information could be gleaned, but from which it was not possible to deduce a complete structure. Preliminary hydrolytic and catalytic reduction experiments did not yield encouraging results. The complete structure of xenicin was elucidated by single crystal x-ray diffraction and is shown in 1. This formula also connotes the absolute configuration derived from crystallographic data. A stereoview' of xenicin is shown in Figure 1. Bond distances, bond angles, and torsion angles are given in Figures 2, 3, and 4. Xenicin possesses a dihydropyran ring trans-fused to a nine-membered carbocyclic ring and represents the first member of a hitherto unknown skeletal system.8 The ninemembered ring contains a trans double bond with a torsion angle of - 158' and an exocyclic double bond. Bond lengths and torsion angles indicate that the nine-membered ring is slightly strained. No short intermolecular distances were found in the crystal structure. The NMR chemical shift assignments and proton couplings in 1, confirmed by double irradiation experiments at 100 and 220 MHz, are shown in Table 1. The enol ether proton H(3) exhibits allylic coupling to H(4a), but not to the conformationally mobile H(12). At 220 MHz (benzene-d6) the H(9) signal is clearly visible as a broadened triplet, J = 7 Hz, indicating a coupling of nearly 7 Hz with one of the C( 10) protons and only a very small coupling to the other as would be suggested by the conformation of crystalline 1.
/ 99:17 / August 17,1977
5781
Figure 1. Stereoview of single molecule. The nine largest atoms are oxygen.
/‘.496131
/1.347131
26
22
Figure 2. Bond distances with standard deviations for last digit in parentheses.
Figure 4. The torsion angles in the two rings. The vertical elevations describe the dista,nces from the least-squares plane through both rings.
Table I. N M R Chemical Shift and Multiplicity Data for Xenicin (1)
Solvent
Proton
C6D6
CDCIj
Multiplicity, J [coupling proton(s)]
6.10 5.87 d, 2 [H(1 la)] d, 2 [H(4a)] 6.65 6.58 2.26 2.19 br d, 8-9 [H(9)] 5.42 5.27 5.75 5.70 br t, 8-9 [H(8), one H ( IO)] 1.85 1.88 5.62 5.38 d, 9-10 [H(13)] 6.10 5.82 t, 9-10 [H(12), H(14)] 5.08 5.08 br d, -10 [H( 13); H ( 16,17)] (1.53, 1.84) (1.74, 1.84)
34-
1.48 4.91 1.60 (3) 1.74 (9)
22
1.73 4.82, 4.96 2.04 (3) 2.06 (6) 2.08 (3)
are searching for compounds related to xenicin which might provide some insight into this question.
Figure 3. Bond angles. Standard deviations for the bond angles are between 0.18 and 0.25’.
The biosynthesis of xenicin may involve cyclization of geranylgeraniol in a manner analogous to that proposed9 for caryophyllene and related compounds, followed by oxidative cleavage of the resulting cyclobutane ring and eventual closure of the dihydropyran ring. However, a more direct formation of the nine-membered ring can be envisioned as occurring via oxidative cyclization of geranyllinalool as outlined below. We
I
Schmitz, van der Helm, et al.
/
Xenicin
5782
Experimental Section Melting points were taken on an A. H. Thomas Unimelt apparatus and are uncorrected. Infrared spectra were taken on a Beckman IR-8 spectrophotometer. N M R spectra were acquired on Varian T-60, X L - I 00, or HR-220 spectrometers in the solvents specified; signals are reported in parts per million (a) downfield from internal tetramethylsilane. Low resolution mass spectra were obtained on a Hitachi RMU-7 spectrometer. Chromatographic supports were Florisil (Fisher Scientific, 100-200 mesh) and silica gel for thin layer chromatography (type 60; E M Reagents distributed by Brinkmann Instruments, Inc.). Elemental analyses were performed by Mr. E. Meier, Department of Chemistry, Stanford University, Stanford, Calif. Isolation of Xenicin (1). To approximately 2 Ib (wet weight) of Xenia elongata collected at Heron Island, Australia and preserved in 2propanol was added water to give an approximately 1 / I water/alcohol mixture. The specimens were allowed to soak for a day after the dilution with water, then the solids were separated by filtration, the 2-propanol evaporated under reduced pressure. and the residual water removed by lyophilization.'0 The resulting light brown residue, 58.6 g was extracted with distilled hexane in a Soxhlet extractor and the hexane solubles were chromatographed on Florisil using chloroform to give I .2 g of a brown solid. Rechromatography of this material on 40 g of thin-layer mesh silica gel using ethyl acetate/benzene ( 1 /9) as eluent (20" fractions) gave 357 mg of a white solid, homogeneous by TLC, in the 1 1-15th fractions. Recrystallization of this solid from benzene/hexane afforded 295 mg of xenicin (1): mp 141S 1 4 2 . 3 "C; '(D -36.7" (0.61, CHC13); IR (KBr) 2980,2940,2860, 1735 (br), 1700(sh), 1665. 1635, 1440, 1375. 1235 (vs), 1205, 1180, 1155, 1005,930, 870; mass spectrum (70 eV) 518 (3) (M+), 459 (6), 458 (2). 400 (3), 399 ( 5 ) , 398 (51,392 (52), 391 (21), 339 ( 5 ) , 338 (4), 305 (8). 297 (3), 296 (4), 290 ( 5 ) , 289 (29), 248 (8), 229 (37). 21 1 (51,201 (9), 185 ( 5 ) , 183 (7), 173 (8), 159 (7), 145 (7), 135 (8), 131 (71, I19 (8), 105 ( I l ) , 9 7 (15),93 ( I I ) , 91 ( I I ) . 85 (35),83 (20),78 (23), 69 ( l 7 ) , 60 ( 1 I ) , 5 5 ( l 7 ) , 45 (12). 43 ( I O O ) , and 41 (19). Anal. Calcd for C~xH3809:C, 64.86; H, 7.38; M+ 518.251 58. Found C, 64.90; H , 7.37; M+ 518.248 88. Crystallization and Crystal Data. Needle-like crystals were obtained from a benzene/hexane solution of the compound. The data crystal was cut from a needle and had the shape of a rectangular parallelepiped with an approximate volume of 0.26 mm3. A separate crystal having a similar shape and an approximate volume of 0.03 n1m3 was used in the Friedel pair determination of the absolute configuration. The crystal data at - 160 "C are: C28H3809; M = 51 8.6; monoclinic; a = 17.704 (3). b = 9.061 ( 2 ) ,c = 18.656 (4) A;@= 113.33 (2)'; V = 2748.0 A3; Z = 4; Pcalcd ( - I 60 " C ) = I ,254, P&d (room temp) = 1.207. P&,d (room temp) = 1.197 g cm-): the unit cell dimensions a t room temperaturearea = 1 8 . 0 7 3 ( 2 ) , b = 9 . 1 8 3 ( 1 ) , c = 18.855(3) A, 0= I 13.92 ( I ) " ; F(000) = 1 1 12; space group C2 as confirmed by structure determination; nickel filtered Cu Ka radiation; X(Cu K a l ) 1.540 51 8, for 20 data and X(Cu KC) 1.5418 8, for intensity data; ~ ( C KC?) U = 7.8 cm-I. The cell parameters were determined by a least-squares fit to the h28 values of 32 reflections distributed throughout all of reciprocal space. The observed density was measured by the flotation method in a mixture of hexane and carbon tetrachloride. The crystal was cooled in a stream of cold nitrogen gas. The temperature was measured as -160 "C. with maximum variations of 2
Table 111. Final Fractional Coordinates ( X IO4) and Isotropic Thermal Parameters for Carbon Atomso ~~
a
X
Y
Z
B , A2
9643 ( I ) 8859 ( I ) 8654 ( I ) 9330 ( I ) 9087 (1) 9043 ( I ) 8328 (1) 8207 (1) 8549 ( I ) 8459 ( I ) 8163 ( I ) 7347 ( I ) 6793 (1) 6315 ( I ) 6245 (2) 5789 (2) 9832 (1) 7835 ( I ) 11092 ( 1 ) 1 I824 (2) 6939 ( I ) 6030 (2) 8896 ( 1 ) 9264 (2) 6923 ( I ) 6599 (1) 8796 (1) 9125 (11
-6098 (3) -7721 (3) -6684 (2) -4257 (3) -2597 (3) -1813 (3) -1827 (3) -1582 (3) -2865 (3) -4385 (3) -7210 (2) -6399 (2) -6640 (3) -5615 (3) -4042 (3) -601 1 (3) -1212 (3) -5277 (3) -5695 (3) -5889 (3) -266 (3) -439 (3) -8240 (3) -7882 (3) -6275 (3) -7174 (3) -5059 (2) -4802 (21
7060 ( I ) 7468 ( I ) 7866 ( I ) 8555 (1) 8548 (1) 7818 (1) 7191 (1) 6356 (1) 6032 ( I ) 6339 (1) 8316 (1) 8108 (1) 7271 (1) 6787 ( I ) 6993 (2) 5953 (2) 7809 (1) 5938 (1) 7695 ( I ) 8449 (2) 5785 (1) 5334 (2) 9585 (1) 10438 ( I ) 9183 ( I ) 9673 ( I ) 7784 ( I ) 7134 (11
1.31 (3) 1.33 (3) 1.18 (3) 1.32 (3) 1.35 (3) 1.30 (3) 1.31 (3) 1.33 (3) 1.43 (3) 1.28 (3) 1.24 (3) 1.30 (3) 1.48 (3) 1.67 (3) 2.36 (4) 2.45 (4) 1.60 (3) 1.59 (3) 1.73 (4) 2.04 (4) 1.51 (3) 1.98 (4) 1.54 (3) 1.85 (4) 1.40 (3) 1.68 (4) 1.13 (3) 1.22 (31
Standard deviation for last digit is in parentheses.
OC. The intensities of all 3015 unique reflections with 0 < 75" were measured on a Nonius CAD-4 automatic diffractometer using a 8-28 scan technique. The scan widths (A@)were adjusted to the dispersion and calculated with the formula A8" = (1.2 0.12 tan e)', for each reflection. A horizontal receiving aperture with a variable width [width (mm) = 4 0.86 tan 01, and height of 6 mm was located 173 mm from the crystal. A reflection was scanned for a maximum of 60 s, with two-thirds of the time spent on scanning the peak (P) and one-sixth of the time spent on each the high 0 and low 8 backgrounds ( L H and RH). The unscaled intensities ( I ) were calculated as I = P - 2 ( R H LH). A standard reflection was monitored after every 20 measurements. The orientation of three reflections was automatically checked after every 100 measurements. A new orientation matrix was automatically obtained if the 20, o,4, or x angle of these reflections was changed by more than 0.1 '. There were 47 reflections which could not be distinguished from the background on the basis that the intensity ( I ) was less than 2(T)ll? ( T = [P 2(RH LH)]). These reflections were assigned intensities equal to 1.41 T ' i z for the purpose of least-squares refinement. Lorentz and polarization corrections were applied to the data. Each amplitude
+
+
+
+
+
Table 11. Final Fractional Coordinates and Anisotrooic Thermal Parameters for Oxveen Atomso
O(2) O(20) O(23) O(24) O(27) O(28) O(31) O(32) O(35)
X
I'
9272 ( I ) 10394 ( 1 ) 1 I IO7 ( 1 ) 7322 ( 1 ) 7282 ( 1 ) 8612 ( I ) 8841 ( I ) 6963 ( I ) 7127 ( 1 )
-7493 (2) -6166 (2) -5206 (3) -1583 (2) 885 (2) -7014 (2) -9466 (2) -7083 (2) -4992 (2)
L'l I
Z
6989 7762 7107 5889 6026 9153 9312 8594 9301
(I) (I) (I) (1)
(I) (1) (1) (1) (1)
232 (8) 163 (7) 360 (1 1) 166 (7) 234 (8) 185 (8) 303 (9) 190 (7) 349 (9)
c'22
u33
u23
171 (8) 269 (8) 497 (14) 187 (8) 213 (9) 162 (7) 196 (8) 185 (8) 233 (9)
241 (7) 210 (7) 317 ( I O ) 224 (7) 324 (9) 168 (7) 253 (9) 204 (7) 335 ( I O )
-28 (7) 45 (7) 28 ( I O ) 16 (7) -18 (7) 8 (6) 40 (7) -22 (6) -73 (8)
The x , y , and z (all X104) are fractional coordinates. The anisotropic parameters (A2, all X103) are used in the expression: exp U33I2c** 2iY12hka*b* 2U13hla*c* 2U23klb*c*)]). Standard deviation for the last digit is in paren( - [ 2 ~ ~ ( U l l h ~ a U2zk2b*2 *~ theses.
+
+
+
Journal of the American Chemical Society
+
+
/ 99:17 / August 17, 1977
5783 Table IV. Final Fractional Coordinates (X103) and Isotropic Thermal Parameters for Hydrogen Atomso
H(11) H(31) H(5 1) H(52) H(61) H(62) H@l) ~(91) H(101) H ( 102) H(121) H(131) H(141) H(161) H ( 162) H(163) H(171) H ( 172) H ( 173) H(181) H ( 182) H(183) H(191) H(192) H(221) H(222) H(223) H(261) H(262) H(263) H(301) H(302) H(303) H(341) H(342) H(343) H(401) H(411) ~I
975 (2) 872 (2) 929 (2) 989 (2) 942 (2) 858 (2) 784 (2) 842 (2) 828 (2) 914 (2) 805 (2) 743 (2) 681 (2) 640 (3) 567 (3) 650 (3) 519 (2) 584 (2) 594 (3) 1009 (2) 1024 (2) 976 (2) 776 (2) 740 (2) 1177 (4) 1186 (2) 1233 (2) 595 (2) 582 (3) 579 (3) 949 (3) 967 (3) 883 (2) 643 (3) 703 (2) 611 (3) 822 (2) 953 i2j
a. A2
V
Z
-596 (4) -875 (4) -476 (4) -437 (4) -214 (4) -258 ( 5 ) -219 (4) -66 (4) -290 (4) -276 (4) -830 (4) -543 (4) -758 (4) -348 (6) -385 ( 5 ) -385 (6) -583 (4) -681 (4) -542 (6) -49 ( 5 ) -197 ( 5 ) -67 (4) -6 19 (4) -510 (4) -541 (8) -696 (4) -543 ( 5 ) - 1 19 (4) 40 ( 5 ) -96 ( 5 ) -687 (6) -859 (6) -798 ( 5 ) -648 ( 5 ) -778 ( 5 ) -767 (7) -453 (4) -402 (3) ~,
659 (2) 747 (2) 903 (2) 860 (2) 905 (2) 860 (2) 728 (2) 623 (2) 547 (2) 616 (2) 823 (2) 825 (2) 709 (2) 668 (2) 685 (3) 749 (3) 584 (2) 584 (2) 559 (3) 824 (2) 790 (2) 733 (2) 613 (2) 545 (2) 881 (3) 865 (2) 841 (2) 507 (2) 499 (2) 562 (2) 1057 (2) 1067 (3) 1065 (2) 998 (3) 1001 (2) 935 (3) 761 (2) 729 (2) ~,
X
2.0 (6) 1.5 (6) 1.9 (6) 1.5 (6) 1.3 (5) 2.9 (8) 1.4 ( 5 ) 1.3 ( 5 ) 1.8 (6) 2.4 (7) 1.4 (6) 1 .o ( 5 ) 1.3 ( 5 ) 4.0 (9) 4.0 (9) 4.4 (10) 2.7 (7) 1.6 (6) 4.2 (9) 3.0 (8) 3.4 (8) 1.6 (6) 1.5 (6) 1.8 (6) 6.0 (3) 1.5 (6) 3.0 (8) 2.6 (7) 3.8 (9) 4.4 (10) 4.3 (10) 5.0 ( 1 1) 3.0 (8) 4.2 (10) 3.2 (8) 5.9 (13) 1.4 (6) 0.9 (~, 5)
Standard deviation for last digit is in parentheses.
was assigned an experimental weight based on counting statistics.’] Structure Determination and Refinement. Phase determination was carried out with the p_rogram M-ULTAN’~using the 300 E values > I .5. The reflections 16 2 9 and 3 1 5 were used to define the origin. Three general reflections and one special reflection were permitted to generate 128 phase sets. As expected for a space group having no translational symmetry elements, the absolute figure of merit of the phase set yielding the solution was one of the lower values.12The coordinates of all nonhydrogen atoms were generated by M U L T A N and refined isotropically with block-diagonal (9 X 9) least-squaresI3 methods using isotropic temperature factors. All hydrogen atom positions were either determined from geometrical considerations or located in a difference Fourier and were included in the refinement. The oxygen atoms were given anisotropic temperature factors, and after the absolute configuration was assigned (vide infra) the observed structure factors were corrected14 for the anomalous scattering of Cu radiation by the oxygen atoms. None of the carbon atoms showed anisotropic motion in the difference Fourier synthesis. Atomic and anomalous scattering factors for carbon and oxygen were taken from the “International Tables for X-ray Crystallography” and those for hydrogen from Stewart, Davidson, and Simpson.I6 The refinement was terminated when all shifts were
